The Karmanos Cancer Institute (KCI) is a charitable 501(c)(3) organization affiliated with Wayne State University (WSU) dedicated to cancer care, research, and education with the ultimate goal to eradicate this disease. Our catchment area includes the four-county area of Wayne, Oakland, Macomb, and Monroe, a population of 4.0 million. The demographic makeup of metropolitan Detroit, which in its entirety is within our catchment area, is 82.7% African American. The demographic makeup of our entire catchment area is 24.3% African American. The nearby city of Dearborn includes the largest concentration of Arabs outside the Middle Eastern countries. Challenges and opportunities facing both us and the City of Detroit include the economy (unemployment is 9.8%, 38.1% live below the poverty level) and education (47.0% of the adult population are functionally illiterate). Cancer rates in our catchment area generally outpace state and national rates. In calendar year 2013, KCI?s inpatient and ambulatory facilities (KCH) cared for a total of 6,013 new patients (2,420 registered cancer patients by NCI?s definition) with 29.4% representing minority groups. In the same year, our minority accrual to interventional treatment protocols was 27.4%. We have a long standing scientific and patient care commitment to the African American population of southeastern Michigan, as exemplified in the broad array of studies focused on molecular, therapeutic, and social disparities. This application profiles the strengths and successes of our four scientific Programs, Tumor Biology and Microenvironment (TBM, 01), Molecular Imaging (MI, 02), Molecular Therapeutics (MT, 03), and Population Studies and Disparities Research (PSDR, 04). Nine Shared Resources are proposed, one of which is a new Shared Resource. The Center?s total annual direct project funding is $56,240,646 (an increase of 5.1% over the 2010) of which $30,685,044 is peer reviewed funding. Of peer reviewed funding, $16,235,791 is from the NCI. Over the next grant period, KCI aims to substantially participate in our Nation?s efforts to: 1) Discover molecules, mechanisms, and pathways that contribute to the causes, progression, and evasion from therapeutic interventions of cancer with special attention to racial, ethnic, and socioeconomic factors as process modifiers; 2) Develop molecules, devices, models, tools, and approaches that lead to an effective reduction in cancer risk, tissue invasion, and metastatic spread, as well as enhancement of communication with and engagement of patients, their families and care providers, and communities at large; and 3) Deliver promising novel therapies and interventions to the population of Michigan through our distributed network of 18 cancer care delivery sites that cover 48 of the 83 counties of Michigan with special attention to racial and ethnic minorities, as well as socioeconomically disadvantaged groups.